Biomedical subjects
Publications and source records attributed to John W Winkelman.
Despite advances in the management of restless legs syndrome (RLS), there still is a great deal of uncertainty about its etiology, pathophysiology, therapy, and clinical outcomes. Much remains to be learned. Future research on these issues will help identify the optimum therapeutic approach for the diverse group of patients with RLS.
BACKGROUND AND PURPOSE: The aim of this study was to estimate the prevalence of restless legs syndrome (RLS) symptoms in the US adult population and to relate frequency of RLS symptoms to self-reported general health, depressive and anxiety symptoms, daytime sleepiness, and cardiovascular disease. PATIENTS AND METHODS: Data were obtained from a survey, conducted in 2002, of 2821 participants in the Wisconsin Sleep Cohort, a prospective community-based epidemiology study. Classification of RLS symptoms was based on the following four symptoms at the 2002 survey: 'repeated urge to move your legs' and 'strange and uncomfortable feelings in the legs', 'when sitting or lying down' which occur at least weekly, 'get better when you get up and start walking' and 'disrupt your sleep'. RESULTS: Prevalence of RLS symptoms occurring at least weekly was 10.6%, with no statistical difference between males (9.9%) and females (11.2%). Individuals with symptoms of RLS occurring at least weekly were older than those without such symptoms (P<0.02). Those with Daily RLS symptoms had statistically more frequent excessive daytime sleepiness, poorer self-reported general health, an elevation in depressive and anxiety symptoms, and an increased prevalence of cardiovascular disease compared to those with no RLS symptoms. All of these associations were stronger in subjects with Daily RLS symptoms than those with RLS symptoms 1-6 times per week. CONCLUSIONS: RLS symptoms are associated with multiple physical and psychological indices of impaired health. Longitudinal studies are required to determine whether RLS symptoms are causally related to excessive daytime sleepiness, poor general health, elevated depression and anxiety symptoms, and cardiovascular disease.
Parasomnias are undesirable behaviors that arise from sleep but are not fully under voluntary control. Parasomnias are grouped broadly according to whether they arise from non-rapid eye movement (NREM) or rapid eye movement (REM) sleep. NREM parasomnias are disorders of arousal that occur along a continuum of behavioral, affective, and autonomic activation. REM-related parasomnias include REM sleep behavior disorder, sleep paralysis, and nightmare disorder. Parasomnias can often be managed successfully using behavioral and pharmacologic therapies.
STUDY OBJECTIVE: This study compares the heart rate responses to the termination of respiratory events, both with and without associated leg movements. METHODS: Heart rate was measured for 15 R-R intervals before (T-15 to T-1) and after (T+1 to T+15) the termination of respiratory events as a change from the baseline rate, defined as the average of 10 R-R intervals occurring before the termination of each respiratory event (T-15 to T-6). Individual heart rate changes of the 21 patients were then averaged separately for 10 respiratory events with and 10 without associated leg movements. SETTING: N/A. PARTICIPANTS: Twenty-one patients with obstructive sleep apnea who had respiratory events both with and without associated leg movements. INTERVENTION: N/A. RESULTS: Maximal heart rate rise for respiratory events with leg movements (7.9 beats per minute) was significantly greater than for respiratory events without leg movements (5.1 beats per minute) (p < .0001). The area under the curve for heart rate increase from T-5 to T+9 was 50.1% higher for respiratory events with leg movements than without leg movements. When respiratory events with and without accompanying leg movements were compared, there were no significant differences in mean duration of respiratory events, mean oxygen desaturation after respiratory events, mean duration of electroencephalogram arousal following respiratory events, or mean heart rate during the baseline period. Heart rate rise did correlate with duration of the leg movements (p < .001) in those respiratory events with leg movements. CONCLUSIONS: Cardiac activation is significantly greater when the termination of respiratory events is associated with leg movements compared to those without leg movements. This exaggerated heart rate response may be an independent consequence of the leg movements themselves, as other features of the respiratory events and associated arousal were not different in the two conditions.
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OBJECTIVE: Determine the efficacy and tolerability of topiramate in the treatment of sleep-related eating disorder (SRED). METHOD: This is a retrospective chart review of consecutive patients treated in an open-label trial of topiramate for SRED in a sleep disorders clinic. Patients were diagnosed according to the second edition of the International Classification of Sleep Disorders. Patients with a Clinical Global Impressions of Improvement (CGI-I) rating of "very much" or "much" improved were considered treatment responders. RESULTS: 30 subjects were prescribed topiramate, of whom 25 had at least 1 postbaseline follow-up appointment. The mean age of these 25 patients was 44 +/- 12 years, 76% were female, and the mean age at onset of SRED was 25.2 +/- 12.8 years. The mean dose of topiramate was 135 +/- 61.6 mg (range, 25-300 mg) over a mean period of 11.6 +/- 11.4 months (range, 1-42 months). Over two thirds of the patients (17/25 or 68%) were considered topiramate responders. Twenty-eight percent (7/25) of the patients lost more than 10% of body weight. Adverse events were reported by 84% (21/25) of patients. Nearly half (7/17 or 41%) of the responders discontinued topiramate after a mean of 12.4 months. CONCLUSION: In this open-label retrospective trial, topiramate was found to be very effective in reducing nocturnal eating in patients with chronic SRED. The tolerability of topiramate was an issue in some patients. Given the promise of this approach, but the limitations of this study, prospective, double-blind study of topiramate in a larger sample of patients with SRED is warranted.
This study aimed to investigate the relationship between measures of clinical symptom severity and sleep EEG parameters in a relatively diagnostically homogeneous group of patients with schizophrenia. We obtained sleep EEG data in 15 drug-free inpatients who met DSM-IV-R criteria for schizophrenia, undifferentiated type, with 15 age- and sex-matched normal controls over two consecutive night polysomnographic recordings. Clinical symptoms were assessed by the Positive and Negative Symptom Scale (PANSS) and Hamilton Rating Scale for Depression. Characteristic features of sleep disturbance were seen in patients with schizophrenia: profound difficulties in sleep initiation and maintenance, poor sleep efficiency, a slow wave sleep (SWS) deficit, and an increased REM density. SWS was inversely correlated with cognitive symptoms. REM density was inversely correlated with positive, cognitive, and emotional discomfort symptoms as well as PANSS total score. Our data demonstrate that drug-free patients with chronic undifferentiated type schizophrenia suffer from profound disturbances in sleep continuity and sleep architecture. Both the SWS deficit and cognitive impairment found in schizophrenics in this study may relate to similar underlying structural brain abnormalities.
BACKGROUND: Frequent electroencephalographic arousals or awakenings associated with periodic leg movements (PLM) might be responsible in part for the complaints of sleep disturbances made by patients treated with antidepressants. Past studies, however, have determined the effects of only certain limited antidepressants, generally in small numbers of subjects, and never in a head-to-head study. METHODS: A total of 274 consecutive patients taking antidepressants and 69 control subjects not taking antidepressants met criteria among patients referred for overnight diagnostic polysomnography. Periodic leg movements were visually counted and the PLM index (PLMI) was calculated. RESULTS: The venlafaxine and selective serotonin reuptake inhibitor (SSRI) groups had significantly higher mean PLMIs than control and bupropion groups. Periodic leg movement indexes at thresholds considered to be of potential clinical significance were more statistically prevalent in the SSRI and venlafaxine groups compared with the control and bupropion groups. The odds ratio of having a PLMI greater than 20 was 5.15 for the SSRI group and 5.24 for the venlafaxine group compared with the control group. CONCLUSIONS: Venlafaxine and SSRI-induced PLM are likely to be the result of enhanced serotonergic availability and secondarily decreased dopaminergic effects. The results of this study might assist in the selection of antidepressants, especially in patients with pronounced sleep complaints.
STUDY OBJECTIVES: To review the literature on restless legs syndrome (RLS), periodic limb movements in sleep, and depression. DESIGN: Literature review. SETTING, PARTICIPANTS, AND INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: We conducted a comprehensive review of the literature searching for publications that included data on depression or antidepressants and RLS or periodic limb movements in sleep. Sixty-two relevant literature references were found and reviewed. Four population-based studies and 9 clinical studies reported significantly higher rates of depression symptoms in individuals with RLS than in controls. Conversely, the prevalence of RLS in patients presenting with depression was reported as elevated in 2 studies. Conflicting data were found regarding the effect of antidepressants on the sensory symptoms of RLS. In contrast, several studies have found that selective serotonin reuptake inhibitor antidepressant use is associated with increased periodic limb movements in sleep. CONCLUSIONS: Depression symptoms are common in adults with RLS. However, the relationship appears complex, with overlap between RLS- and depression-related symptoms confounding the issue. Given what is known at this time, we propose a specific treatment approach to patients with RLS and depression symptoms.
STUDY OBJECTIVES: Rapid eye movement (REM) sleep behavior disorder (RBD) is generally observed in older men and in individuals with specific neurologic diseases. There are case reports of RBD in individuals taking serotonergic antidepressants. Our objective was to assess electromyogram (EMG) activity during REM sleep in individuals taking serotonergic antidepressants and in a matched control group not on such medication. DESIGN: Chart review of clinical and polysomnographic data. SETTING: Sleep laboratory affiliated with a general hospital. PARTICIPANTS: 15 subjects taking a serotonergic antidepressant and 15 age-matched individuals not on such medication. MEASUREMENTS: Submental and anterior tibialis tonic and phasic EMG activity during REM sleep, REM latency, time in REM, apnea-hypopnea index, periodic leg movements of sleep index, and sleep-architecture measures. RESULTS: Tonic, but not phasic, submental EMG activity during REM sleep was significantly more common in the antidepressant-treated group than in the control group (P < .02). Tonic REM submental EMG activity correlated with REM latency (r = .42, P = .02) and inversely with REM time (r = -.36, P = .05). Subject age correlated with tonic REM submental EMG activity (r = .58, P = .02) in the antidepressant group There were also trends for more phasic activity in the anterior tibialis (P = .09) and submental (P = .07) EMG in REM sleep in the antidepressant group than in the control group. CONCLUSIONS: Subjects taking serotonergic antidepressants had more EMG activity in the submental lead during REM sleep than did controls. This correlated with measures of REM suppression and age. Individuals taking such medications may be at increased risk of developing REM sleep behavior disorder, particularly with increasing age.
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BACKGROUND: Dopaminergic agents have become first-line treatments for restless legs syndrome (RLS). The most common serious complications of L-Dopa treatment of RLS are "augmentation", in which RLS symptoms appear earlier during the day, and tolerance, in which medication effectiveness wanes over time. The aims of this study were to assess rates of augmentation and tolerance, and their interrelationship, with pramipexole treatment of RLS. PATIENTS AND METHODS: Retrospective assessment of all patients (N=59) treated for RLS with pramipexole for at least 6 months (mean duration=21.2+/-11.4 months) by the senior author. Pramipexole dosing and clinical follow-up were performed in a standardized fashion. L-Dopa was discontinued and other medications for RLS were tapered as tolerated. Rates of augmentation (need for earlier administration of the same dose of pramipexole) and tolerance (need for an increase in pramipexole dose) were determined. RESULTS: Augmentation developed in 32% (19/59), and tolerance occurred in 46% (27/59), of patients. These two complications were statistically related (P<0.05). The only clinical predictors of these complications were previous augmentation or tolerance to L-Dopa. CONCLUSIONS: Augmentation and tolerance are more common with extended pramipexole treatment of RLS than has been previously reported in preliminary studies. However, these complications are generally manageable by earlier dosing or small dose increases of this agent, and only rarely require medication discontinuation.
BACKGROUND: Sleep-related eating disorder (SRED) and nocturnal eating syndrome (NES) combine features of sleep disorders and eating disorders. Treatment of these nocturnal eating behaviors has been directed towards underlying identifiable sleep or eating disorders using dopaminergic or opioid agonists, as well as anorectic agents, at times with the addition of sedatives. METHODS: Two patients with SRED and two with NES, who had failed multiple previous trials of pharmacotherapy and psychotherapy, were treated in a naturalistic, open-label fashion with topiramate at night. Reduction in nocturnal eating was graded based on self-report. Weight was computed at the outset of, and during, topiramate treatment. RESULTS: One patient with NES had a complete elimination of nocturnal eating with topiramate, two patients (one with NES, one with SRED) had a marked response, and one patient (with SRED) had a moderate response. Mean dose was 218 mg, though three patients noted an improvement at 100 mg. Notable weight loss was observed in all patients (mean of 11.1 kg). Benefits of topiramate treatment have been maintained for a mean period of 8.5 months. CONCLUSIONS: Topiramate may be of benefit for patients with NES or SRED in reducing nocturnal eating, improving nocturnal sleep, and producing weight loss.
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